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Identification of natural inhibitors to inhibit C. acnes lipase through docking and simulation studies

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Abstract 

Acne vulgaris is a common skin disease affecting 80–90% of teenagers worldwide. C. acnes producing lipases are the main virulence factor that catalyzes sebum lipid into free fatty acid that is used for C. acnes growth. Recently, computational biology and bioinformatics play a significant role in drug discovery programs and the identification of novel lead(s). In this study, potential inhibitors against the C. acnes lipase have been identified via cost-effective computational investigations. Molecular docking, MD simulations, and binding affinity analysis have been performed between the active site of C. acnes lipase protein and selected natural plant constituents. First, C. acnes lipase protein was downloaded from PDB and defined the catalytically active site. Next, 16 active natural plant constituents were shortlisted from the PubChem library (based on their pharmacokinetics, pharmacodynamics, and antibacterial activity). Docking studies identified the best five active compounds that showed significantly strong binding affinity interacted through hydrogen bonding, hydrophobic interactions, and π-stacking with the active site residues of the target protein. Furthermore, a 100 ns MD simulation run showed a stable RMSD and less fluctuating RMSF graph for luteolin and neryl acetate. In silico investigation suggested that luteolin, neryl acetate, and isotretinoin were involved in stable interactions which were maintained throughout the MD run with the C. acnes lipase enzyme, virtually. The results advocated that these could potentially inhibit lipase activity and be used in the clinical management of acne.

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Acknowledgements

The author is greatly acknowledged and thankful to the director of CSIR-IGIB for providing the research facility and carrying out research work and manuscript writing.

Funding

The author (APS) received a Senior Research Fellowship (31/0430410)/2019-EMR-I) and research support (OLP-1149) from the Council of Scientific & Industrial Research (CSIR), India. Co-authors (HA and VS) received Research Associate Fellowships (ISRM/11(35)/2019, 5519–2019/CMB-BMS respectively) from the Indian Council of Medical Research (ICMR), India.

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Authors and Affiliations

  1. CSlR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, 110025, India

    Akash Pratap Singh, Vijay Singh, Pradeep Kumar & Hemant K. Gautam

  2. Academy of Innovative and Scientific Research (AcSIR), Ghaziabad, 201002, India

    Akash Pratap Singh, Pradeep Kumar & Hemant K. Gautam

  3. Department of Biotechnology, Central University of Rajasthan, Ajmer, India

    Hemant Arya

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  1. Akash Pratap Singh
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  2. Hemant Arya
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Contributions

APS designed and conducted all the experiments and wrote the manuscript. Editing was done by VS and HA. All authors read and approved the final version of the manuscript.

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Correspondence to Hemant K. Gautam.

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Singh, A.P., Arya, H., Singh, V. et al. Identification of natural inhibitors to inhibit C. acnes lipase through docking and simulation studies. J Mol Model 28, 281 (2022). https://doi.org/10.1007/s00894-022-05289-3

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